Structure-Guided Bacteria Specificity and Wide Activity Spectrum of Endotoxin-Responsive Peptide Nanonets

IF 9.6 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2024-10-21 DOI:10.1021/acs.nanolett.4c03166

Nhan Dai Thien Tram, Jan Kazimierz Marzinek, Louis Perrin, Devika Mukherjee, Vanitha Selvarajan, Peter John Bond, Pui Lai Rachel Ee

{"title":"Structure-Guided Bacteria Specificity and Wide Activity Spectrum of Endotoxin-Responsive Peptide Nanonets","authors":"Nhan Dai Thien Tram, Jan Kazimierz Marzinek, Louis Perrin, Devika Mukherjee, Vanitha Selvarajan, Peter John Bond, Pui Lai Rachel Ee","doi":"10.1021/acs.nanolett.4c03166","DOIUrl":null,"url":null,"abstract":"Peptide nanonets offer a promising avenue for constructing anti-infective biomaterials. Our group recently reported innovative designs of synthetic BTT nanonets that fibrillate selectively in response to bacterial endotoxins. Herein, we delved deeper into the molecular interactions between our peptides and these bacteria-specific biomolecules, which is an aspect critically missing from major works in the field. Using microscopic and biophysical techniques, we identified phosphate moieties in endotoxins as being the most essential to the initiation of peptide fibrillation. This was strongly supported by molecular dynamics simulations in an outer membrane environment with variable states of phosphorylation. To support the claim over bacterial specificity, we demonstrated a lack of nanonet formation in the presence of various phosphate-containing biomolecules native to human biology. The structural importance of phosphate moieties among pathogenic strains strongly indicates a wide clinical spectrum of our peptides, which was experimentally verified.","PeriodicalId":53,"journal":{"name":"Nano Letters","volume":null,"pages":null},"PeriodicalIF":9.6000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nano Letters","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1021/acs.nanolett.4c03166","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

Peptide nanonets offer a promising avenue for constructing anti-infective biomaterials. Our group recently reported innovative designs of synthetic BTT nanonets that fibrillate selectively in response to bacterial endotoxins. Herein, we delved deeper into the molecular interactions between our peptides and these bacteria-specific biomolecules, which is an aspect critically missing from major works in the field. Using microscopic and biophysical techniques, we identified phosphate moieties in endotoxins as being the most essential to the initiation of peptide fibrillation. This was strongly supported by molecular dynamics simulations in an outer membrane environment with variable states of phosphorylation. To support the claim over bacterial specificity, we demonstrated a lack of nanonet formation in the presence of various phosphate-containing biomolecules native to human biology. The structural importance of phosphate moieties among pathogenic strains strongly indicates a wide clinical spectrum of our peptides, which was experimentally verified.

Abstract Image

查看原文本刊更多论文

内毒素响应肽纳米网的结构引导细菌特异性和广泛活性谱

肽纳米网为构建抗感染生物材料提供了一条前景广阔的途径。我们的研究小组最近报告了合成 BTT 纳米网的创新设计，这种纳米网在细菌内毒素的作用下会选择性地纤维化。在此，我们深入研究了我们的肽与这些细菌特异性生物分子之间的分子相互作用，这是该领域主要研究中严重缺失的一个方面。利用显微镜和生物物理技术，我们确定了内毒素中的磷酸分子是引发肽纤维化的最重要因素。在磷酸化状态可变的外膜环境中进行的分子动力学模拟有力地证明了这一点。为了支持细菌特异性的说法，我们证明了在人类生物学中存在各种含磷生物大分子的情况下，纳米网的形成并不存在。病原菌中磷酸盐分子结构的重要性有力地说明了我们的多肽具有广泛的临床应用范围，这一点已得到实验验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.